I have had the opportunity to develop a clinical research career in HIV in women and more specifically on HIV-1 shedding in the female genital tract. The purpose of this application for a Mid-career Investigator Award in Patient-Oriented Research (K24) is to provide the framework within which I can mentor junior clinical investigators in patient-oriented research focused on critical issues related to HIV in women. This proposal builds on the existing resources at our institution that has a robust track record of training junior faculty to become independent investigators. Our institution is committed to research training that can prepare the next generation of physicians to bridge the gaps in our knowledge in HIV infection. The Division of Infectious Diseases at the Miriam Hospital, Brown Medical School, includes NIH funded Adult AIDS Clinical Trials Unit, the Brown/Tufts/Lifespan Center of AIDS Research, the AIDS International Training and Research Program, the Center for Drug Addiction and AIDS Research, and NIH funded training grants. About 37-40 million adults are estimated to be living with HIV/AIDS and half of these are women. The predominant mode of HIV transmission worldwide is through heterosexual contact. Although many factors are associated with sexual transmission of HIV-1 (both behavioral and biologic), HIV-1 viral load has been identified as the chief predictor of the risk of sexual transmission. Levels of HIV-1 viral load have been associated with mother-to-infant transmission of HIV. Several studies have also shown a good correlation between blood plasma viral load and male and female genital tract viral load. The use of antiretroviral medications can reduce blood plasma HIV-1 RNA levels as well as genital tract HIV-1 RNA. Studies have also shown a reduction in perinatal transmission with effective antiretroviral therapy. Transmission of drug resistant HIV-1 has been reported in the US and Europe ranging from 2% to 27% among newly infected patients. There have been reports of resistant genotypic variants in both male and female genital tract that is different from those of blood. These findings underscore the risk of spreading resistant HIV-1 variants sexually as well as perinatally. With my research, I hope to be able to help contribute to the work on HIV treatment and prevention.